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Métodos Terapéuticos y Terapias MTCI
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1.
Medicina (Kaunas) ; 56(12)2020 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-33321982

RESUMEN

Background and objectives: Chrysanthemum zawadskii var. latilobum (CZ), which has traditionally been used as a oriental tea in Asia, is known to have anti-inflammatory effects in osteoarthritis (OA). But the mechanism of these effects has not been made clear and it needs to be elucidated specifically for the clinical use of CZE in OA. Materials and Methods: To reveal this mechanism, we first identified which biomarkers were expressed in the joints of rats in which OA had been induced with monosodium iodoacetate and determined whether CZ extract (CZE) could normalize these biomarkers in the progression of OA. The anti-osteoarthritis effect of CZE was evaluated for its capability to inhibit levels of extracellular matrix (ECM)-degrading enzymes and enhance ECM synthesis. We also sought to identify whether the marker compound of CZE, linarin, has anti-osteoarthritic effects in the human chondrosarcoma cell line SW1353. Results: The changes in matrix metalloproteinases (MMPs) were remarkable: among them, MMP-1, MMP-3, MMP-9 and MMP-13 were most strongly induced, whereas their expressions were inhibited by CZE dose dependently. The expressions of the ECM synthetic genes, COL2A1 and ACAN, and the transcription factor SOX9 of these genes were reduced by OA induction and significantly normalized by CZE dose dependently. SOX9 is also a repressor of ECM-degrading aggrecanases, ADAMTS-4 and ADAMTS-5, and CZE significantly reduced the levels of these enzymes dose dependently. Similar results were obtained using the human chondrosarcoma cell line SW1353 with linarin, the biologically active compound of CZE. Conclusions: These anti-osteoarthritic effects suggest that CZE has mechanisms for activating ECM synthesis with SOX9 as well as inhibiting articular ECM-degrading enzymes.


Asunto(s)
Chrysanthemum , Osteoartritis , Animales , Condrocitos , Humanos , Interleucina-1beta , Osteoartritis/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas
2.
Biol Pharm Bull ; 42(12): 1988-1995, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31787714

RESUMEN

Rich in bioactive substances such as amino acids and peptides, Laennec (human placenta hydrolysate) has been widely used to control various types of musculoskeletal pain. However, the effects of Laennec on tendon and ligament injuries are not clearly understood. In the present study, Laennec was tested to identify its in vivo effects on ligament injury in an animal model and its in vitro effects on tendon-derived fibrocytes. A total of 99 Sprague Dawley rats were divided into the negative control (normal) group (n = 11) and the ligament injury group (n = 88). The ligament injury group was subdivided into normal saline-treated group, Laennec-treated group, polydeoxyribonucleotide-treated group, and 20% dextrose-treated group. Ligaments were collected at 1 week and 4 weeks after treatment. Histologic and biomechanical properties were analyzed. In vitro effects of Laennec and polydeoxyribonucleotide on fibrocytes were also analyzed. Although all other treatment groups showed increased inflammatory cells, the Laennec-treated group maintained cell counts and activated macrophage levels that were similar to the normal group. Unlike the saline-treated group and dextrose-treated group, the Laennec-treated group had low levels of degenerative changes at 4 weeks after treatment. Supportively, in vitro results showed that the Laennec-treated group had increased collagen type I, scleraxis (Scx) and tenomodulin (Tnmd) expression (p < 0.05). Our study demonstrates that Laennec treatment enhances wound healing of damaged ligament by suppressing immune responses and reducing degenerative changes of damaged ligament. In addition, we found that Laennec induces the gene expression of type I collagen, Scx and Tnmd in fibrocytes, suggesting that Laennec may facilitate regeneration of damaged ligaments. Therefore, we expect that Laennec can be a useful drug to treat injured ligament.


Asunto(s)
Mezclas Complejas/farmacología , Ligamentos/efectos de los fármacos , Ligamentos/lesiones , Placenta/química , Tendón Calcáneo/citología , Animales , Femenino , Humanos , Ligamentos/inmunología , Ligamentos/fisiología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Embarazo , Ratas Sprague-Dawley , Resistencia a la Tracción
3.
J Med Food ; 22(2): 140-151, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30676853

RESUMEN

The gastroprotective effects of BST-104 (a water extract of Lonicera japonica) and the mechanisms involved were investigated in murine models of gastritis and peptic ulcer. The gastroprotective effects of BST-104 and its active components were evaluated in rat models of HCl/ethanol-induced gastritis and acetic acid-induced gastric ulcer. After orally administering BST-104, chlorogenic acid, rebamipide (positive control), or vehicle to each animal model, gastric lesion sizes, gastric mucus statuses, proinflammatory cytokine levels, and oxidative stress were measured. Superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) levels and oxidized/reduced glutathione (GSH) ratios in gastric mucosal tissues were measured to evaluate oxidative stress. To clarify the action mechanism of BST-104, we investigated nuclear factor (NF)-κB pathway involvement by real-time polymerase chain reaction (PCR). In the acetic acid-induced ulcer model, oral administration of BST-104 at 50, 100, or 200 mg/kg significantly reduced gastric lesions by 38%, 43%, and 55%, respectively, compared with vehicle controls. BST-104 significantly increased gastric mucus contents and this was accompanied by higher levels of hexosamine, sialic acid, and prostaglandin E2 in gastric mucus. Furthermore, BST-104 treatment increased antioxidant activities, as evidenced by higher levels of catalase, SOD, and oxidized/reduced GSH and lower MDA levels. In addition, BST-104 significantly suppressed proinflammatory cytokine (tumor necrosis factor-α, interleukin [IL]-6, and IL-1ß) increases, and real-time PCR showed that BST-104 significantly downregulated NF-κB expression. In summary, BST-104 and its active component, chlorogenic acid, were found to have gastroprotective effects by virtue of their antioxidant and anti-inflammatory properties through downregulation of NF-κB expression.


Asunto(s)
Antiinflamatorios/farmacología , Antiulcerosos/farmacología , Antioxidantes/uso terapéutico , Ácido Clorogénico/farmacología , Lonicera/química , Extractos Vegetales/farmacología , Estómago/efectos de los fármacos , Ácido Acético , Animales , Antiinflamatorios/uso terapéutico , Antiulcerosos/uso terapéutico , Antioxidantes/metabolismo , Antioxidantes/farmacología , Ácido Clorogénico/uso terapéutico , Citocinas/sangre , Etanol , Gastritis/inducido químicamente , Gastritis/tratamiento farmacológico , Gastritis/metabolismo , Ácido Clorhídrico , Masculino , Moco/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Ratas Sprague-Dawley , Estómago/patología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico
4.
Biol Pharm Bull ; 41(8): 1257-1268, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29794403

RESUMEN

Chrysanthemum zawadskii var. latilobum (CZ) has been used as a traditional medicine in Asian countries for the treatment of inflammatory diseases. Recently, CZ extract was shown to inhibit differentiation of osteoclasts and provide protection against rheumatoid arthritis. The aim of this study was to investigate the molecular mechanisms of BST106, the ethanol extract of CZ, for cartilage protection in monosodium iodoacetate (MIA)-induced osteoarthritis (OA), particularly focusing on apoptosis and autophagy. BST106 (50, 100, and 200 mg/kg) was orally administered once daily to MIA-induced OA rats. Swelling, limping, roentgenography, and histomorphological changes were assessed 28 d after MIA injection. Biochemical parameters for matrix metalloproteinase (MMP), apoptosis, and autophagy were also assessed. BST106 ameliorated the severity of swelling and limping after MIA injection. Roentgenographic and histomorphological examinations revealed that BST106 reduced MIA-induced cartilage damage. BST106 decreased MIA-induced increases in MMP-2 and MMP-13 mRNA levels. Increased levels of serum cartilage oligomeric matrix protein and glycosaminoglycan release were attenuated by BST106. Furthermore, BST106 suppressed the protein expression of proapoptotic molecules and increased the protein expression of autophagosome- and autolysosome-related molecules. These findings indicate that BST106 protects against OA-induced cartilage damage by inhibition of the apoptotic pathway and restoration of impaired autophagic flux.


Asunto(s)
Chrysanthemum , Osteoartritis/tratamiento farmacológico , Extractos Vegetales , Sustancias Protectoras , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Cartílago Articular/patología , Ácido Yodoacético , Articulación de la Rodilla/efectos de los fármacos , Articulación de la Rodilla/metabolismo , Articulación de la Rodilla/patología , Masculino , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/genética , Osteoartritis/inducido químicamente , Osteoartritis/metabolismo , Osteoartritis/patología , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Conejos , Ratas Sprague-Dawley
5.
Xenobiotica ; 44(12): 1099-107, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24933530

RESUMEN

1. BST204, a purified ginseng dry extract containing a high concentration of racemic Rh2 and Rg3 mixtures, is being developed for supportive care use in cancer patients in Korea. This study investigates the pharmacokinetics and tissue distribution of BST204 in rats. 2. After oral administration of BST204, only the S epimers, S-Rh2 and S-Rg3, could be determined in rat plasma. The poor absorption of the R-epimers, R-Rh2 and R-Rg3, may be attributed to lower membrane permeability and extensive intestinal oxygenation and/or deglycosylation into metabolites. The AUC and Cmax values of both S-Rh2 and S-Rg3 after BST204 oral administration were proportional to the administered BST204 doses ranged from 400 mg/kg to 2000 mg/kg, which suggested linear pharmacokinetic properties. 3. There were no statistically significant differences in the pharmacokinetics of S-Rh2 and S-Rg3 after oral administration of pure S-Rh2 (31.5 mg/kg) and S-Rg3 (68 mg/kg) compared with oral administration of BST204, 1000 mg/kg. These indicated that the presence of other components of BST204 extract did not influence the pharmacokinetic behavior of S-Rh2 and S-Rg3. 4. After oral dosing of BST204, S-Rh2 and S-Rg3 were distributed mainly to the liver and gastrointestinal tract in rats. 5. Our finding may help to understand pharmacokinetic characteristics of S-Rh2, R-Rh2, S-Rg3, and R-Rg3, comprehensively, and provide useful information in clinical application of BST204.


Asunto(s)
Ginsenósidos/farmacocinética , Extractos Vegetales/administración & dosificación , Administración Oral , Animales , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Ginsenósidos/administración & dosificación , Ginsenósidos/química , Ginsenósidos/metabolismo , Masculino , Estructura Molecular , Extractos Vegetales/metabolismo , Ratas , Ratas Sprague-Dawley
6.
Food Chem Toxicol ; 68: 117-27, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24632066

RESUMEN

We evaluated the potential of BST204, a purified dry extract of ginseng, to inhibit or induce human liver cytochrome P450 enzymes (CYPs) and UDP-glucuronosyltransferases (UGTs) in vitro to assess its safety. In vitro drug interactions of four bioactive ginsenosides of BST204, S-Rg3, R-Rg3, S-Rh2, and R-Rh2, were also evaluated. We demonstrated that BST204 slightly inhibited CYP2C8, CYP2D6, CYP2C9, and CYP2B6 activities with IC50 values of 17.4, 26.8, 31.5, and 49.7µg/mL, respectively. BST204 also weakly inhibited UGT1A1, UGT1A9, and UGT2B7 activities with IC50 values of 14.5, 26.6, and 31.5µg/mL, respectively. The potential inhibition by BST204 of the three UGT activities might be attributable to S-Rg3, at least in part, as its inhibitory pattern was similar to that of BST204. However, BST204 showed no time-dependent inactivation of the nine CYPs studied. In addition, BST204 did not induce CYP1A2, 2B6, or 3A4/5. On the basis of an in vivo interaction studies, our data strongly suggest that BST204 is unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most CYPs or UGTs involved in drug metabolism in vivo. Our findings offer a clearer understanding and possibility to predict drug-drug interactions for the safe use of BST204 in clinical practice.


Asunto(s)
Inhibidores Enzimáticos del Citocromo P-450/farmacología , Interacciones Farmacológicas , Inhibidores Enzimáticos/farmacología , Ginsenósidos/farmacología , Glucuronosiltransferasa/antagonistas & inhibidores , Extractos Vegetales/farmacología , Animales , Línea Celular Tumoral , Cromatografía Liquida , Sistema Enzimático del Citocromo P-450/metabolismo , Femenino , Glucuronosiltransferasa/metabolismo , Humanos , Concentración 50 Inhibidora , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem
7.
J Vet Sci ; 11(3): 273-5, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20706037

RESUMEN

Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in a carrageenan-air pouch model. HSE (200 mg/kg, oral) suppressed exudation and albumin leakage, as well as inflammatory cell infiltration. Dexamethasone (2 mg/kg, i.p.) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content. HSE lowered tumor-necrosis factor (TNF)-alpha and nitric oxide (NO), as well as prostaglandin E(2) (PGE(2)). Dexamethasone only reduced TNF-alpha and NO, while indomethacin decreased TNF-alpha and PGE(2). The suppressive activity of HSE on NO and PGE(2) production was confirmed in RAW 264.7. These results demonstrate that HSE exerts anti-inflammatory effects by inhibiting both TNF-alpha-NO and cyclooxygenase II-PGE(2) pathways.


Asunto(s)
Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Transducción de Señal/efectos de los fármacos , Análisis de Varianza , Animales , Carragenina , Línea Celular Tumoral , Dexametasona/farmacología , Dinoprostona/metabolismo , Houttuynia , Técnicas para Inmunoenzimas , Indometacina/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Óxido Nítrico/metabolismo , Irrigación Terapéutica , Factor de Necrosis Tumoral alfa/metabolismo
8.
Reprod Toxicol ; 27(1): 79-84, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19103281

RESUMEN

The effects of green tea extract (GTE) on the fetal development and external, visceral and skeletal abnormalities induced by cyclophosphamide were investigated in rats. Pregnant rats were daily administered GTE (100mg/kg) by gavage for 7 d, from the 6th to 12th day of gestation, and intraperitoneally administered with cyclophosphamide (11mg/kg) 1h after the final treatment. On the 20th day of gestation, maternal and fetal abnormalities were determined by Cesarian section. Cyclophosphamide was found to reduce fetal and placental weights without increasing resorption or death. In addition, it induced malformations in live fetuses; 94.6%, 41.5% and 100% of the external (skull and limb defects), visceral (cleft palate and ureteric dilatation) and skeletal (acrania, vertebral/costal malformations and delayed ossification) abnormalities. When pre-treated with GTE, cyclophosphamide-induced body weight loss and abnormalities of fetuses were remarkably aggravated. Moreover, repeated treatment with GTE greatly increased mRNA expression and activity of hepatic cytochrome P-450 (CYP) 2B, which metabolizes cyclophosphamide into teratogenic acrolein and cytotoxic phosphoramide mustard, while reducing CYP3A expression (a detoxifying enzyme). The results suggest that repeated intake of GTE may aggravate cyclophosphamide-induced body weight loss and malformations of fetuses by modulating CYP2B and CYP3A.


Asunto(s)
Anomalías Inducidas por Medicamentos , Hidrocarburo de Aril Hidroxilasas/biosíntesis , Camellia sinensis/química , Ciclofosfamida/toxicidad , Extractos Vegetales/farmacología , ARN Mensajero/efectos de los fármacos , Teratógenos/toxicidad , Animales , Hidrocarburo de Aril Hidroxilasas/genética , Citocromo P-450 CYP2B1/biosíntesis , Citocromo P-450 CYP2B1/genética , Citocromo P-450 CYP3A/biosíntesis , Citocromo P-450 CYP3A/genética , Sinergismo Farmacológico , Femenino , Desarrollo Fetal/efectos de los fármacos , Desarrollo Fetal/fisiología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Embarazo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley ,
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